1. Field of the Invention
The invention generally relates to improved vaccines against canine parvovirus-like viruses. In particular, the invention provides vaccines suitable for puppies which are based on a novel parvovirus isolated from a raccoon.
2. Background of the Invention
Canine parvovirus (CPV) is primarily an enteric pathogen that infects dogs, especially young dogs. Parvovirus infection is characterized by acute diarrhea, fever and leukopenia in dogs and puppies more than 4 to 5 weeks old, and myocardial disease in younger puppies. The mortality rate from the disease in unvaccinated dogs is very high. While vaccines against CPV are available, because CPV is a single-stranded DNA virus and has an extreme ability to mutate, the virus shows a remarkable ability to vary antigenically (Parrish and Kawaoka 2005) and thereby elude the immune protection afforded by vaccines. Thus, constant monitoring of the antigenic type and genotype of circulating viruses, and adjustment of vaccine components accordingly, is necessary.
Newborn puppies acquire immunities against diseases such as CPV infection by nursing from their mother, especially during the first two days of life. A puppy that nurses takes in colostrum in the milk that is first produced and antibodies in the colostrum are passed to the puppy. For dogs and many other mammals as well, the immunity given by the colostrum loses its affect sometime around the fifth week of age.
A particular challenge when vaccinating puppies is to administer vaccines according to a time frame that provides protection which overlaps the protection provided by maternal antibodies and begins as maternal antibodies wane. Currently, vaccine regimens for puppies typically begin at about 6 weeks of age and boosters are given about every 3 weeks thereafter, e.g. at 9, 12 and 15 weeks. However, in order for this regimen to provide full protection, the first vaccine dose must immediately elicit a protective immune response. This is completely unrealistic due to the immaturity of the puppy's immune system and the time period required to mount an immune response. Full protection usually does not develop until the entire course of vaccinations is given. The age-based mortality due to CPV is depicted in FIG. 1, which shows that maximum mortality due to CPV occurs before vaccine protocols can be completed.
A simple answer might be to begin the vaccination program even earlier, e.g. at 2-3 weeks. However, this would be futile because, for puppies whose mothers have been vaccinated with or otherwise exposed to a viral strain with the same antigenic determinants, maternal antibodies passed to the puppy would neutralize viruses in the vaccine, thereby preventing the puppy's own immune system from responding to the virus.
Another challenge in veterinary medicine is the treatment of cancer, e.g., in dogs. There are many limitations in the existing tools for cancer therapy, especially for geriatric dogs. The administration of oncolytic parvoviruses to kill cancer cells shows great promise as an effective cancer treatment (Rommelaere et al, Cytokine & Growth Factor Reviews 21:185-195, 2010; and U.S. Pat. No. 7,179,456 to Rommelaere et al, the complete contents of which are herein incorporated by reference) and might be applied to canines. However, the existence of pre-existing antibodies to parvoviruses (e.g. as a result of vaccination) would render this method ineffective, since the parvovirus would be neutralized by the existing antibodies. In addition, gene therapy in dogs is rarely undertaken at present but would be a promising method for treating several disorders, if suitable nucleic acid vectors are identified.
The prior art has thus far failed to provide solutions to these problems.